How to manage the patient with a family history of aneurysmal subarachnoid haemorrhage

17 Pages·2004·1.61 MB·English

88 PRACTICAL NEUROLOGY
NEUROLOGICAL DILEMMAS
How to manage
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P. M. White rig
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Consultant Neuroradiologist t.
Department of Clinical Neurosciences, University
of Edinburgh, Western General Hospital,
Crewe Road, Edinburgh, EH4 2XU, UK; E-mail:
[email protected]
Practical Neurology, 2004, 4, 88–103
© 2004 Blackwell Publishing Ltd
APRIL 2004 89
INTRODUCTION WHAT IS THE FREQUENCY OF INTRA-
‘The truth is rarely pure and never simple’. So CRANIAL ANEURYSMS IN THE GENERAL
said Oscar Wilde, and this is certainly the case POPULATION?
for individuals with an unruptured intracranial What is anyone’s risk of harbouring an aneu-
aneurysm or a family history of aneurysmal rysm, after all incidental aneurysms are com- P
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subarachnoid haemorrhage (SAH). Before you monly found at autopsy? Rinkel et al. identifi ed c
can counsel these people, it is fi rst necessary for autopsy studies where the prevalence of unrup- t N
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the clinician to have a grasp of this complex tured aneurysms ranged from 0.4% to 3.6% for uro
asorema ebtheicnagu site coannnceo ty boeu u hnatoveld .t oYlodu tmheig hpta tsiuebn-t rinet rroe taron da pnrdo sppreocstpiveec tsitvued aiensg, iroegsrpaepchtiyv esltyu, danieds l: firs
sequently expand on the information imparted, from 3.7% to 6%, respectively (Rinkel et al. t pu
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but you cannot remove it – correct or incorrect 1998). More recent studies are more in line with lis
‘The truth is rarely h
– from the patient’s mind (Fuller 2001). In this the higher fi gures from the prospective studies e
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article I will summarize the relevant knowledge, (Kojima et al. 1998; Ronkainen et al. 1998). In a a
and offer some advice, on management in this higher-risk group of patients, because they had pure and never s o
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rather fraught area of medicine. already ruptured an aneurysm, 20–25% had at 1
simple’ A
least one unruptured aneurysm on angiography p
(Lozano & Leblanc 1987). So approximately one ril 2
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in 20 of the population aged over 30 harbour an 0
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unruptured aneurysm. However, it is important . D
to remember that, with an aneurysmal SAH in- ow
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cidence of about 8 per 100 000 per annum lo
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(Wardlaw & White 2000), clearly only a very d
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small proportion of these aneurysms actually d
rupture (about 0.1–0.2% pa). fro
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ARE SPECIFIC GROUPS AT PARTICU- ttp
LARLY HIGH RISK OF INTRACRANIAL ://p
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ANEURYSMS? .b
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The risk factors for SAH and for having an j.c
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unruptured intracranial aneurysm are very m
similar (Table 1). In addition, several genetic o/
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conditions are associated with intracranial J
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aneurysms, although these represent less than nu
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10% of all cases: ry
(cid:127) 10–15% of patients with adult polycystic 26
kidney disease (ADPKD) (Rinkel et al. 1998), , 2
0
particularly if there is a family history of 23
There are several stages of assessment and aneurysms and/or SAH (Hughes et al. 1996; by
management to consider: Ruggieri et al. 1994); gu
e
(cid:127) What is an individual’s risk of harbouring an (cid:127) type IV Ehlers–Danlos syndrome (Schievink s
aneurysm? et al. 1990); t. P
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(cid:127) How best to detect an aneurysm without (cid:127) possibly pseudoxanthoma elasticum (Muny- te
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exposing the patient to unnecessary stress or er & Margulis 1981), although this has been te
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risk? refuted (van den Berg et al. 1999); b
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(cid:127) If an asymptomatic aneurysm is found, what (cid:127) hereditary haemorrhagic telangiectsaia c
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is the risk of rupture? (Roman et al. 1978); p
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(cid:127) What treatment, if any, should be offered and (cid:127) neurofi bromatosis type I (Mulvihill et al. rig
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what are the risks involved? 1990; Morooka & Waga 1991); t.
Most importantly, the risk at each stage must be (cid:127) alpha1-antitrypsin defi ciency (Schievink et
weighed against the risk of not doing anything. al. 1996).
The pros and cons of screening for aneurysms Marfan’s syndrome was thought to be associ-
will also be briefl y considered to place some of ated with aneurysms but a detailed study of 135
this information in context. patients (mean age 21 years) found no evidence
© 2004 Blackwell Publishing Ltd
90 PRACTICAL NEUROLOGY
Table 1 Risk factors for intracranial aneurysms, and for subarachnoid haemorrhage
RISK OF PREVALENCE OF RELATIVE
RISK FACTOR ANEURYSM SAH ANEURYSMS RISK REFERENCE
Female gender + + 1.6 Linn et al. 1996
Current smoking + + 1.9 Teunissen et al. 1996 P
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Hypertension – + 2.8 Teunissen et al. 1996 c
Alcohol (heavy consumption) – + 4.7 Teunissen et al. 1996 t N
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Oral contraceptive pill ? + 1.5 (low dose) Johnston et al. 1998 uro
H e avy physical exertion – + 12..97 ((hoidgdhs d roastieo)) Anderson et al. 1993 l: firs
t p
Atherosclerosis ? + 2.3 Rinkel et al. 1998 u
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Ischaemic heart disease in woman + + (4.3) Uehara et al. 1998 lis
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Cholesterol > 6.3 mmol/L ? + 10.2 (odds ratio) Adamson et al. 1994 e
d
Autosomal dominant polycystic + + 10–15% 4.4 Rinkel et al. 1998 a
s
kidney disease o
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Familial (2 or more fi rst- or second- + + 9.8% 4.0 Rinkel et al. 1998 1
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degree relatives) p
First-degree relatives in families + + 4.5% 1.8 see Table 2 ril 2
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with one affected member 0
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of a relationship (van den Berg et al. 1996), (Table 2). The relative risk for SAH in relatives h
although the patients may not have been old compared with the background population was ttp
enough for the aneurysms to have developed. 2.9–6.6 for fi rst-degree relatives and 1.6–2.1 for ://p
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In addition, aneurysmal SAH may affect sev- second degree. Whilst these relative risks appear .b
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eral members of a family without any specifi c large, it is important to remember the small j.c
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genetic ‘disease’. Familial SAH has been defi ned absolute number of relatives affected: only 156/ m
Approximately inconsistently, so here I mean a family in which 21054 (0.74%) fi rst-degree relatives were them- o/
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two or more close blood relatives (fi rst or second selves affected by SAH. In our Scottish study (in J
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one in 20 of the degree) have a history of aneurysmal SAH with- press) the risk of SAH among family members nu
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out any other known heritable disease (fi rst- over the decade after the index case had their ry
population aged degree relatives = parents, siblings, children; SAH was 1.2% for fi rst-degree and 0.5% for 26
second degree = grandparents, grandchildren, second-degree relatives (some 12 and 5 times, , 2
0
over 30 harbour aunts and uncles, nieces and nephews; third respectively, the background population SAH 23
degree = cousins, great grandparents, great risk) (Wardlaw et al., in press). by
an unruptured grandchildren) Familial intracranial aneurysms may have gu
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It has been suggested that many cases of distinguishing biological features, including: s
aneurysm ‘familial intracranial aneurysms’ might simply rupture at a younger age (most frequently in the t. P
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represent accidental aggregation (ter Berg et al. fi fth decade compared to the sixth decade for te
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1992); on the basis of chance alone, each SAH sporadic SAH) (Bromberg et al. 1995); worse te
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patient has a 5.6% possibility of having a fi rst- to clinical outcome; and an increased prevalence b
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third-degree relative also affected by SAH (ter of middle cerebral artery aneurysms (Kojima c
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Berg et al. 1992), and the proportion of SAH et al. 1998; Bromberg et al. 1995). There may p
y
patients with third-degree relatives who had be a younger age of rupture in subsequent rig
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had an SAH is the same as the proportion with generations, implying ‘anticipation’ (Interna- t.
SAH in the control population (De Braekeleer tional Subarachnoid Aneurysm Trial 2002) but
et al. 1996). familial aneurysms may also have a predilection
Since 1987, 10 studies have examined the towards rupture in the same decade in individu-
prevalence of unruptured aneurysms and/or als of the same family, particularly in siblings
SAH amongst relatives of patients with SAH (Leblanc 1997).
© 2004 Blackwell Publishing Ltd
APRIL 2004 91
COMMENT sibs only surveyed – average six per index case 11.4 OR for SAH in 1° relative = 1.8, 2° = 2.4 RR of SAH in 1° relative = 4.1 2° = 1.6 RR of SAH in 1° relative = 6.6 defi nite, and 2.7 possible SAH RR of SAH in 1° relative = 4.7, 2° = 2.1, 3° = 1.1 compared to general pop Risk of unruptured aneurysm in 1° or 2°4x greater than general pop. 3.7% of 1° had an unruptured aneurysm RR 2.9, 4.5 for 77% cases admitted RR 2.3–2.4. Ten year prospective risk 1.2% in 1°, 0.5% in 2° OR for SAH in 1° relative = 4.0 Pract Neurol: first pub
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% 1° WITH SAH 4.7 1.8 1% / 10.6 ¶ 0.6 0.1 2.9 N/S hed a
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OF RELATIVES WIT 2 3° ° / / 16 / 5 / 4 + 12 / ‡ 51 77 37 relatives in total → / / / / 65 / / pril 2004. Downlo
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NUM 1° 22 18 11 10 + 48 76 4 19 87 29 d from
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Table 2Summary of population based studies of familial subarachnoid haemorrhage* NUMBER NUMBER OF RELATIVES SURVE OF INDEX STUDY SUBJECTS LOCATION 1° 2° 3° Norrgard 1987 485 Umea, Sweden 1352 / / (sibs only) Washington, USA N/S N/S N/S Wang 1995 149/171† Rochester, USA 608 N/S N/S Schievink 1995 76/81† Bromberg 1995 163 Utrecht, Netherlands 1290 3588 N/S de Braekeleer 1996 533 (+ 1599 Quebec, Canada N/S N/S N/S controls) 1997 91 Kuopio, Finland 716 relatives in total Ronkainen§→ (1°, 2° and 3°) (2° and 3°) Raaymakers 1999 160 Utrecht, Netherlands 626 / / Gaist 2000 6175 Denmark (1977–95) 14781 / / Davie Cooper Study 453 Scotland 3023 5668 Okamoto 2003 200 Japan N/S / / *Wardlaw in press. number surveyed/total sample available. † defi nite + possible SAH.‡ relatives with SAH or aneurysm.§ % of all relatives not just fi rst degree.¶ OR, odds ratio; RR, relative risk; N/S = not stated / = no data. on January 26, 2023 by guest. Protected by copyright.://pn.bmj.com/
© 2004 Blackwell Publishing Ltd
92 PRACTICAL NEUROLOGY
WHICH RELATIVES ARE MOST risk was 0.07% (Cloft et al. 1999). Non-invasive
FREQUENTLY AFFECTED BY SAH? tests, such as magnetic resonance angiography
In families with more than one person with (MRA), dynamic spiral CT Angiography (CTA)
SAH, the most frequent relationship is index and transcranial Doppler sonography (TCDS)
patient to sibling, followed by index patient to (Fig. 2) are attractive for detecting asympto-
parent (Wardlaw & White 2000). However, a matic intracranial aneurysms but they have to P
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parent was affected in only 29% so in less than be extremely accurate to replace IADSA. So how c
one-third of affected families was there a clear accurate are they? t N
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warning of the potential for SAH from a previ- Analysis of accuracy per patient rather than uro
oa ums ugcehn esrtraotinogne.r I fnatmerielisatiln lignlyk, toon me asttuerdnya flo SuAnHd p‘secrr eaenneinugry’ samn iins doivf imduoarle foclri nainceaul rryeslemvas.n Mceo tsot l: firs
than to paternal or sibling SAH (Okamoto et al. studies reported apparently excellent results but t pu
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2003) and in another study, the slightly more were in patients with a recent SAH so the aneu- lis
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commonly affected fi rst-degree relatives were rysm prevalence was high (Table 4) (White et al. e
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also parents (38%) rather than siblings (33%) 2000). As a result the sensitivities, specifi cities a
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(Wardlaw, in press). Only our Scottish study has and predictive values must be interpreted with o
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prospectively investigated the interaction be- caution, particularly if one is extrapolating to 1
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tween the type of relationship and involvement using the non-invasive test in a low aneurysm p
of more than one family member (with SAH) prevalence population where far more positive ril 2
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on the risk of SAH to the other family members test results will be false positives. Crucially, the 0
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(Table 3). Here, there was a hierarchy of ascend- results for non-invasive imaging methods are . D
ing risk from a second-degree relative and no signifi cantly poorer for aneurysms < 5 mm in ow
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other family members affected (0.3% cumula- size, which constitute as many as one-third of lo
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tive lifetime SAH risk) to the highest risk in a aneurysms in asymptomatic patients (Kojima d
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member of a family with at least two fi rst-degree et al. 1998) (Fig. 3). Sensitivities are in the order d
relatives affected (7% cumulative lifetime SAH of 35%, 57% and 35% for aneurysms < 5 mm fro
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risk) (Wardlaw in press). diameter for MRA, CTA and TCDS, respectively h
(White et al. 2001; White et al. 2001) ICA an- ttp
HOW BEST TO DETECT AN ANEURYSM? eurysms are even harder to detect (White et al. ://p
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The gold standard is an intra-arterial digital 2000, 2001). Ultrasound has the advantage of .b
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subtraction angiogram (IADSA) with selective the lowest capital cost, and portability, and with j.c
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cerebral arterial injections and multiple projec- contrast agents and 3-D imaging the accuracy m
tions, particularly using the 3D DSA technique may improve towards the level of CTA/MRA o/
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(Fig. 1). However, IADSA is invasive, costly, and (Wardlaw & White 2000). Unfortunately, about J
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not without risk of a permanent neurological 10% of patients will not have an adequate bone nu
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complication. In patients with SAH, suspected window and the technique is operator depend- ry
aneurysm or arteriovenous malformation, this ent. 26
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Table 3 Relationship between the family history of an index subarachnoid haemorrhage (SAH) case and the t. P
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risk of SAH to other family members te
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NUMBER OF SAH CUMULATIVE SAH RISK te
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FAMILY HISTORY OF SAH EVENTS OCCURRING (BIRTH TO 70 YEARS) b
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One second-degree relative with SAH 6 0.3% c
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One fi rst-degree relative 7 0.8% py
No fi rst but at least two second-degree relatives 1 1% rig
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One fi rst and at least one second-degree relative 2 2% t.
At least two fi rst-degree relatives 4 7%
Analysis based on 3213 relatives of 148 index cases.
Risk prior to 30 years of age is extremely low.
For comparison, the background population risk of SAH is ~0.06% per decade.
© 2004 Blackwell Publishing Ltd
APRIL 2004 93
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Figure 1 (a) Imaging of a large anterior communicating artery aneurysm (arrow) with standard 2D intra- lo
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arterial digital subtraction angiography (IADSA). By comparison, the 3D IADSA image (b) demonstrates d
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cthaero dteidta airletedr ya nanateoumryys omf *t.he aneurysm, particularly the neck, far more clearly. Note additional right middle d from
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Figure 2 (a) Right terminal carotid bifurcation aneurysm (arrow) demonstrated on 2D intra-arterial digital subtraction angiography (b) MRA y c
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– Maximum Intensity Projection (MIP) and (c) CTA MIP images. This was a ruptured aneurysm and the associated haematoma results in marked T1 p
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breakthrough effect on the MRA MIP image – highlighting the location of the aneurysm. This effect (or the blood distribution on CT) is one reason rig
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why diagnostic accuracy studies on SAH patients cannot be readily extrapolated into the screening context. t.
© 2004 Blackwell Publishing Ltd
94 PRACTICAL NEUROLOGY
More recently there have been further studies more reliably, than less experienced observers
of non-invasive imaging tests vs. IADSA (White (Okahara et al. 2002; White et al. 2003).
et al. 2001a; White et al. 2001b; Okahara et al.
2002; Chung et al. 1999; Jager et al. 2000; Me- IF AN ASYMPTOMATIC ANEURYSM IS
tens et al. 2000; Suzuki et al. 2003; Pedersen et al. FOUND WHAT IS ITS RISK OF RUPTURE?
2001) and a CTA meta-analysis was published in The best available data on rupture risk are sum- P
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2002 (Chappell et al. 2003). These later studies marised in Table 5. A systematic review by Rin- c
have in general been of better quality although kel et al. found an overall annual rupture rate of t N
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there was still a marked preponderance of 1.9% (Rinkel et al. 1998). Aneurysms were twice uro
puantriuenpttsu rwedit ha nSeAuHry srmaths.e rT hthea nse nassyitmivpittioesm aantidc tahs el ikrieslky toof rruuppttuurree iinn cwroeamseedn twhiatnh iang em. eSny manpd- l: firs
specifi cities were similar to those in the earlier tomatic aneurysms were signifi cantly more t pu
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systematic review. Two small studies suggest likely to rupture than incidental or additional lis
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that dynamic contrast MRA (rapid MRA dur- (asymptomatic) aneurysms (6.5% vs. 0.8% vs. e
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ing an intravenous injection of gadolinium) 1.4%, respectively). Posterior circulation and a
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may be more accurate than time of fl ight MRA large (> 10 mm) aneurysms were signifi cantly o
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(Metens et al. 2000; Suzuki et al. 2003), but they more likely to rupture. In a logistic regression 1
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do suffer from the methodological problems of model, the only factor signifi cantly related to p
the early time-of-fl ight MRA studies and might aneurysm rupture was the size of the aneurysm ril 2
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be over-optimistic. Two studies, which looked at – 7 mm or larger aneurysms had a relative risk 0
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the effect of observer experience on aneurysm of rupture of 2.24 compared with smaller aneu- . D
detection found, not surprisingly, that experts rysms (Juvela et al. 1993). Virtually all patients ow
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detected substantially more aneurysms, and in this study had had a previous SAH. In the lo
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Figure 3 (a) Left terminal carotid bifurcation aneurysm (arrow) on 2D intra-arterial digital t.
subtraction angiography. (b) Although the terminal carotid is irregular in appearance, the
very small aneurysm cannot be readily appreciated on the MRA MIP image and even the
base image (c) does not clearly demonstrate the aneurysm – illustrating the problems
of detecting very small aneurysms with non-invasive imaging methods. However, the
aneurysm was detected on transcranial Doppler sonography – arrowed ‘An’ (d).
© 2004 Blackwell Publishing Ltd
APRIL 2004 95
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Table 4 Sensitivity and specifi city of non-invasive tests for intracranial aneurysms (White c
et al. 2000) t N
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MRA (PP)* CTA (PP)† TCDS (PP)‡ MRA (PA)§ CTA (PA)¶ TCDS (PA)** ro
Sensitivity 87 92 – 87 90 82 l: firs
Specifi city 92 94 – 95 86 95 t p
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*926 subjects in 20 studies; †677 subjects in 16 studies; ‡No studies reported data lis
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per patient; §1596 aneurysms in 926 subjects; ¶1582 aneurysms in 677 subjects; **97 e
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aneurysms in 162 subjects. a
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PP, identifi cation of a patient as having or not having an aneurysm; PA, identifi cation of an o
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individual aneurysm correctly; MRA, magnetic resonance angiography; CTA, computerized 1
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tomography angiography; TCDS, transcranial Doppler sonography. p
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Table 5 Summary of data on annual risk of rupture of unruptured aneurysms . D
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INTERNATIONAL STUDY OF INTERNATIONAL STUDY OF UNRUPTURED
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UNRUPTUREDINTRACRANIAL ANEURYSMS INTRACRANIAL ANEURYSMS lo
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RINKEL ET AL. 1998* & INVESTIGATORS 1998 (RETROSPECTIVE) & INVESTIGATORS 2003 (PROSPECTIVE) e
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No. of subjects 95 1449 1692 (unoperated cohort) fro
No. of aneurysms – 193 686 m
Duration of follow-up 3907 h
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(patient years) (mean of mean follow-ups 5.5, 12023 7587 ://p
range 2.1–13.7 years) (mean 8.3 years) (mean 4.5 years) n
Number ruptured 75 32 51 .bm
Overall rupture rate (% pa) 1.9 0.27 0.67 j.c
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Rupture rate m
< 10 mm 0.7 0.05 < 7 mm all sites no prior SAH ~0.07 o/
n
> 10 mm 4.0 0.5 < 7 mm all sites prior SAH ~0.41 J
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> 7 mm all sites all patients ~0.1† n
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Cumulative aneurysm 10% per decade 0.5–5% per decade 0.7–1.5% per decade† ry
rupture rate 2
6
(from Juvela et al. 1993) , 2
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Incidental aneurysm 6.5 data not extractable data not extractable 2
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rupture rate b
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Asymptomatic aneurysm 0.8 but 7/8 ruptures in data not extractable < 7 mm ~0.07 g
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rupture rate aneurysms > 10 mm > 7 mm ~2.1 e
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Asymptomatic aneurysm 1.4 data not extractable ~0.36 all sizes t. P
rupture rate ro
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Posterior circulation aneurysm 4.4 data not extractable 0.5 (< 7 mm) – 10% (> 24 mm) c
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rupture rate d
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Age y
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20–39 0 data not extractable data not extractable o
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40–59 3.5 y
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60–79 5.7 h
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*Additional data to that published in the systematic review were kindly supplied by Dr Gabriel Rinkel to allow calcuation of duration of follow up.
The paper by Juvela et al. 1993 contributed 28% of the patients to the systematic review but almost half the patient-years of follow up.
†No difference in rates between groups for larger aneurysms.
The rupture rate is much higher than the combined overall fi gure for the subgroups of posterior circulation aneurysms > 7 mm and for anterior
circulation aneurysms > 12 mm.
© 2004 Blackwell Publishing Ltd
96 PRACTICAL NEUROLOGY
same study, repeat angiography during follow- those with prior SAH, the rupture risk was 0.3%
up showed, in patients with later SAH, that the pa for aneurysms < 7 mm with no signifi cant
size of the aneurysms had increased from the difference from the no SAH group for larger
start of follow-up, whereas in those without aneurysms (International Study of Unruptured
later SAH the size did not change, and new an- Intracranial Aneurysms & Investigators 2003).
eurysms formed during the study in 19%, giving 49/51 ruptures occurred within fi ve years of P
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an approximate rate of formation of 2.2% per diagnosis and only 2/41 ruptures in the no c
year (Juvela et al. 1993). prior SAH group were of aneurysms < 7 mm t N
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Rinkel et al. (pers. comm.) identifi ed a total (both were posterior circulation aneurysms), uro
oalfs 1w1i4th5 ayseyamrs potfo pmaatiteicn ta nfoeluloryws-mups ainnd in ndoi vpirdiuo-r cIto ims wpaorretdh nwoitthin 7g /t1h0a ti na ntehuorsyes mwist h< p2 rmiomr S wAeHre. l: firs
SAH (the group we are really looking at in this arbitrarily excluded from ISUIA, though these t pu
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article). 93% of the aneurysms were 10 mm or can rupture. lis
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less in size. There were nine ruptures – and all e
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but one occurred in aneurysms 10 mm or larger. WHAT TREATMENT, IF ANY, SHOULD BE a
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Thus, the annual rupture rate for asymptomatic OFFERED AND WHAT ARE THE RISKS o
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aneurysms 10 mm or less was about 0.1%. INVOLVED? 1
A
The International Study of Unruptured Whether any treatment for an asymptomatic p
Intracranial Aneurysms (ISUIA) is the largest aneurysm should be offered or not depends ril 2
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ever study to follow up unruptured aneurysms critically on the balance between the long-term 0
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(International Study of Unruptured Intracra- rupture risk (i.e. untreated natural history risk) . D
nial Aneurysms & Investigators 2003). Some vs. the immediate treatment risk. Both of these ow
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patients had asymptomatic aneurysms with no risks in turn depend on the age, gender and life- lo
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prior SAH, and others had previously sustained style factors of the individual patient. d
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SAH from another aneurysm. In the retrospec- d
tive arm, there was a tiny rupture risk of 0.05% Treatment risks fro
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per annum for small aneurysms (< 10 mm Aneurysms are treated by surgical clipping or h
diameter) in patients who had not had an SAH by interventional neuroradiology – coiling. ttp
previously, and of 0.5% per annum for large A systematic review of surgical treatment for ://p
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aneurysms and all aneurysms in patients who unruptured aneurysms identifi ed 61 studies .b
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had previously sustained an SAH (International between 1966 and 1996, but only eight were j.c
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Study of Unruptured Intracranial Aneurysms prospective and unfortunately, in virtually all, m
& Investigators 1998). This 0.05% risk is in the neurosurgeon performing the operation o/
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fact quite similar to the re-calculation of the was also the observer of outcome (Raaymakers J
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rupture risk of 0.1% for aneurysms < 10 mm et al. 1998). Permanent morbidity occurred in nu
a
from Rinkel′s systematic review (Rinkel et al. 10.9% of patients and the case fatality was 2.6%. ry
1998). In the patients that had not previously The lowest morbidity and mortality was found 26
had an SAH, only 1/12 aneurysmal ruptures with small anterior circulation aneurysms (case , 2
0
occurred of an aneurysm < 10 mm in diameter fatality 0.8%, morbidity 1.9%), and the high- 23
(of concern to us in this article), compared with est with large posterior fossa aneurysms (case by
17/20 patients in those who had previously had fatality 9.6%, morbidity 38%). The lack of in- gu
e
an SAH (International Study of Unruptured In- dependent outcome assessment and the effect s
tracranial Aneurysms & Investigators 1998). of publication bias must have underestimated t. P
ro
The more robust prospective data in ISUIA, the surgical risk. The prospective arm of ISUIA te
c
albeit based on rather small numbers, suggest a (Fig. 4) found the surgery-related case fatality te
d
negligible rupture risk for anterior circulation at 1 years was 2.7% in patients with no prior b
y
aneurysms < 7 mm in those without prior SAH SAH and 0.6% in patients who had previously c
o
(none ruptured), 0.5% pa for anterior circula- suffered SAH. Morbidity was the same at 10% p
y
tion aneurysms 7–12 mm, but substantially (International Study of Unruptured Intracra- rig
h
higher risk for larger anterior circulation aneu- nial Aneurysms & Investigators 2003). Age was t.
rysms (3–8% pa). The relative risk of rupture for the only independent predictor of outcome:
posterior circulation (including posterior com- surgery-related morbidity and mortality at
municating) aneurysms was 3–3.2 compared one year was about fi ve times higher in those
with anterior circulation aneurysms of the > 64 years of age compared with patients <
same size. Of no direct concern to this article, in 45 years of age (International Study of Unrup-
© 2004 Blackwell Publishing Ltd
APRIL 2004 97
35 tured Intracranial Aneurysms & Investigators
Clipping
1998).
Coiling
30
The effectiveness and risks of aneurysm
25 coiling in unruptured aneurysms are less cer-
tain because the technique is newer and still
Combined 20
death/disability developing. Guigliemi detachable coils (GDC) P
rate ra
15 were introduced in 1991 and revolutionised the c
endovascular treatment of intracranial aneu- t N
10 e
rysms (Guglielmi et al. 1991) (Fig. 5). System- uro
5 a4t8i cs truevdiieews (sa ollf oanbeseurrvyastmio cnoaill,i nmgo hstalvye r iedternostipfi eecd- l: firs
0 ≤ 12 mm > 12 mm ≤ 12 mm > 12 mm tive) including 1383 patients – but these were t pu
Anterior circulation Posterior circulation b
predominantly of ruptured aneurysms (Brilstra lis
h
et al. 1999). Permanent complications (death/ e
Figure 4 Treatment risks for unruptured aneurysms (adapted from the d
disability) occurred in 3.7%. However, only a
ISUIA data) s
54% of aneurysms were completely occluded o
n
after one procedure, although 88% were sub- 1
A
stantially (> 90%) coiled (Brilstra et al. 1999). p
The re-bleeding rate from partially treated an- ril 2
0
eurysms is higher, and partial occlusion is well 0
4
recognised to be more common with coiling . D
than clipping. The technology of coils and coil- ow
n
ing assist devices is improving all the time, so the lo
a
partial occlusion rate is likely to decline. d
e
There is only one large randomised trial d
that has compared coiling with clipping – the fro
m
International Subarachnoid Aneurysm Trial h
(ISAT) – but only in ruptured aneurysms (Inter- ttp
There is a negligible risk of rupture of national Subarachnoid Aneurysm Trial 2002). ://p
n
This demonstrated a relative risk reduction in .b
m
anterior circulation aneurysms < 7mm death/dependency for coiling over clipping of j.c
o
23% at one year – an absolute risk reduction of m
in those without prior subarachnoid 7%. Most ISAT patients had anterior circula- o/
n
tion aneurysms < 10 mm so the trial was not J
a
haemorrhage completely representative of the generality of nu
a
aneurysms. However, anterior circulation an- ry
eurysms < 12 mm accounted for about 65% of 26
the unoperated subjects and 67% of the surgi- , 2
0
cally treated individuals in ISUIA (International 23
Study of Unruptured Intracranial Aneurysms & by
Investigators 2003). The prospective ISUIA data gu
e
on treatment outcomes are interesting although s
directly comparing clipping and coiling is dif- t. P
ro
fi cult because patient characteristics differ be- te
c
tween the cohorts. There were proportionately te
d
far more elderly patients, posterior circulation b
y
and large aneurysms (all predisposing to poorer c
o
outcome) in the endovascular cohort. Never- p
y
theless, for those with no prior SAH the com- rig
h
bined morbidity and mortality at 1 year was t.
12.6% for clipping and 9.8% for coiling – a 22%
relative risk reduction. For prior SAH patients
at one year the relative risk reduction was 30%
(7.1% vs. 10.1%).
© 2004 Blackwell Publishing Ltd